PMID- 35716147
OWN - NLM
STAT- MEDLINE
DCOM- 20220920
LR  - 20221230
IS  - 1528-1167 (Electronic)
IS  - 0013-9580 (Print)
IS  - 0013-9580 (Linking)
VI  - 63
IP  - 9
DP  - 2022 Sep
TI  - Cortical neuronal hypertrophy and mTOR pathway activation in CAN regions in 
      SUDEP.
PG  - 2427-2438
LID - 10.1111/epi.17335 [doi]
AB  - OBJECTIVES: Dysfunctional connectivity and preexisting structural abnormalities 
      of central autonomic network (CAN) regions have been shown on magnetic resonance 
      imaging (MRI) in sudden unexpected death in epilepsy (SUDEP) and may be 
      mechanistically relevant. In a previous postmortem study we reported increased 
      microglia in CAN regions, including the superior temporal gyrus (STG) in SUDEP. 
      In this current study we investigated mammalian target of rapamycin (mTOR) 
      pathway activation and neuronal c-Fos activation in CAN regions in SUDEP compared 
      to control groups. METHODS: In a series of 59 postmortem cases (SUDEP, n = 26; 
      epilepsy controls [EPCs], n = 14; and nonepilepsy controls [NECs], n = 19), we 
      quantified pS6-240/4, pS6-235/6 (markers of mTOR activation) and c-Fos neuronal 
      densities and labeling index in the STG, anterior cingulate, insula, frontobasal, 
      and pulvinar regions using immunohistochemistry with whole-slide automated image 
      analysis. RESULTS: Significantly more pS6-positive neurons were present in the 
      STG in cases with a history of recent seizures prior to death and also in SUDEP 
      compared to other cause of death groups. No differences were noted for c-Fos 
      neuronal labeling in any region between cause of death groups. Cortical neuronal 
      hypertrophy in the STG was observed in some SUDEP cases and associated with 
      pS6-240/4 expression. pS6-235/6 highlighted neuronal intranuclear inclusions, 
      mainly in SUDEP cases and in the STG region. SIGNIFICANCE: Neuronal labeling for 
      pS6 in the STG correlated with both seizure activity in the period prior to death 
      and SUDEP. Further investigations are required to explore the significance of 
      this region in terms of autonomic network dysfunction that may increase the 
      vulnerability for SUDEP.
CI  - (c) 2022 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of 
      International League Against Epilepsy.
FAU - Patodia, Smriti
AU  - Patodia S
AUID- ORCID: 0000-0003-1981-770X
AD  - Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of 
      Neurology, London, UK.
FAU - Lim, Yau Mun
AU  - Lim YM
AUID- ORCID: 0000-0002-8774-9537
AD  - Department of Neurodegeneration, UCL Queen Square Institute of Neurology, London, 
      UK.
FAU - Chung, Freda
AU  - Chung F
AD  - Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of 
      Neurology, London, UK.
FAU - Stylianou, Irene
AU  - Stylianou I
AD  - Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of 
      Neurology, London, UK.
FAU - El Hachami, Hanaa
AU  - El Hachami H
AD  - Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of 
      Neurology, London, UK.
FAU - Thom, Maria
AU  - Thom M
AUID- ORCID: 0000-0001-7712-2629
AD  - Department of Clinical and Experimental Epilepsy, UCL Queen Square Institute of 
      Neurology, London, UK.
LA  - eng
GR  - U01 NS090405/NS/NINDS NIH HHS/United States
GR  - U01 NS090415/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220708
PL  - United States
TA  - Epilepsia
JT  - Epilepsia
JID - 2983306R
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - *Autonomic Nervous System Diseases
MH  - Death, Sudden/etiology
MH  - *Epilepsy
MH  - Humans
MH  - Hypertrophy/complications
MH  - Neurons/pathology
MH  - *Sudden Unexpected Death in Epilepsy
MH  - TOR Serine-Threonine Kinases
PMC - PMC9795893
OTO - NOTNLM
OT  - C-Fos
OT  - SUDEP
OT  - mTOR
OT  - superior temporal gyrus
COIS- None of the authors has any conflict of interest to disclose.
EDAT- 2022/06/19 06:00
MHDA- 2022/09/21 06:00
PMCR- 2022/12/28
CRDT- 2022/06/18 10:02
PHST- 2022/06/14 00:00 [revised]
PHST- 2022/02/10 00:00 [received]
PHST- 2022/06/15 00:00 [accepted]
PHST- 2022/06/19 06:00 [pubmed]
PHST- 2022/09/21 06:00 [medline]
PHST- 2022/06/18 10:02 [entrez]
PHST- 2022/12/28 00:00 [pmc-release]
AID - EPI17335 [pii]
AID - 10.1111/epi.17335 [doi]
PST - ppublish
SO  - Epilepsia. 2022 Sep;63(9):2427-2438. doi: 10.1111/epi.17335. Epub 2022 Jul 8.